THE INFLUENCE OF NIFEDIPINE AND CAPTOPRIL ON LIVER BLOOD-FLOW IN HEALTHY-SUBJECTS

Aims Application of single methods to assess liver blood flow (LBF) yi elded conflicting results on the magnitude and duration of effect on L BF of oral nifedipine and captopril. The aim of this study was to inve stigate the influence of these drugs on LBF by simultaneous use of ICG infusion and echo-Doppler. Methods The study was performed according to a double-blind, placebo-controlled, randomized, cross-over design i n nine healthy male volunteers. After an overnight fast and an equilib ration period, subjects received a continuous i.v. indocyanine green ( ICG) infusion for 4 h. At presumed ICG steady state (t=45 min), subjec ts were dosed with oral nifedipine (20 mg), captopril (50 mg) or place bo. During the experiment, blood sampling for ICG assay and measuremen t of portal venous blood flow (echo-Doppler) took place regularly. Tre atments were compared using analysis of variance. Differences are repo rted with 95% confidence intervals (CI). Results The area under the cu rves (AUC) for ICG over 1 h and over 3 h after nifedipine were 15% (di fference in AUG: +0.6, +7.0 mg l(-1) min) and 22% (+7.0, 1 +28.4 mg l( -1) min) lower compared with placebo. After captopril, the AUC values were 8-10% lower compared with placebo but the 95% CIs included zero. Portal venous flow was 15% (+5, +86 ml min(-1)) higher compared to pla cebo after nifedipine but not after captopril (-3%; -49, +33 ml min(-1 ). The duration of effect on liver blood flow lasted approximately 2 h but was variable (range: 40-160 min). The time to maximal blood flow increase and the duration of effect after nifedipine were very similar for both measures of LBF. Changes in ICG concentrations could be reas onably well predicted from the changes in portal blood flow. Conclusio ns Nifedipine increases LBF for a substantial period of time but the e ffect is variable between subjects. This effect could be detected by b oth the ICG method and echo-Doppler and the findings of both methods w ere in agreement. In this respect it is likely that captopril does not influence LBF in healthy volunteers as no effect was detected with ei ther method.